Immune Regulation of Extrathymic T (NK1.1^+T) Cells in Parasitic Infection

寄生虫感染中胸腺外 T (NK1.1^ T) 细胞的免疫调节

基本信息

批准号：
08670276
负责人：
SEKIKAWA Hiroho
金额：
$ 1.34万
依托单位：
NIIGATA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670276/
关键词：
Hepatic lymphocyte Extrathymic T cells Host defense Murine Malaria Self-reactive forbidden clones Cytotoxicity against malaria infected red blood cells Leishmaniasis Visceral larve migrans 原虫感染ネズミマラリア蠕虫感染イヌ蛔虫 IL-4産生細胞サイトカイン産生

项目摘要

In a series of recent studies, we have demonstrated that the liver is an important immune organs that produces extrathymic T cells in mice and humans. These T cells are distinguished from thymus-derived T cells by many properties. Some of these properties include the intermediate density of TCR-CD3 complex on their surface and constitutive expression of interleukin-2Rbeta-chain.The development of protective immunity to parasitic infection requires the presence of T cells. In this project, we investigated the role of extrathyinic T cells in mice during infection with murine malaria (P.yoelli), Leishmania (L.major) and Ascaris larvae (T.canis).1) Visceral larva migrans model In early phase of T.canis infection (on day 1), unique population of hepatic T cells were observed, i.e., double-positive (DP) CD4^+CD8^+ cells. The proportion of extrathymic T cells was also elevated therafter.2) Leishmaniasis model In mice infected with L.major, the levels of extrathymic T cells in the liver increased. The produciblity of IL-4 in these T cells elevated in the liver. These observations indicate that the induction of Th2 type immune response is dominant in murine Leishmaniasis.3) Murine malaria model Expansion of extrathymic T cells were observed with flowcytometric analysis of lymphocytes from liver, spleen and thymus. They possessed self-reactive forbidden clones and cytotoxicity against parasitized RBC.Deletion of TL-2Rbeta^+ cells resulted in early exacerbation of infection of the non-lethal strain malaria. These data indicate the extrathymic T cells play a role during the erythrocytic stage of the rodent malaria infection.These results suggest that the expanding extrathymic T cells in various organs play an important role of protective immunity during parasitic infection.

在最近的一系列研究中，我们证明肝脏是小鼠和人类体内产生胸腺外 T 细胞的重要免疫器官。这些 T 细胞与胸腺来源的 T 细胞有许多特性不同。其中一些特性包括其表面 TCR-CD3 复合物的中等密度和白细胞介素 2Rβ 链的组成型表达。针对寄生虫感染的保护性免疫的发展需要 T 细胞的存在。在本项目中，我们研究了小鼠体内胸腺外 T 细胞在感染鼠疟疾 (P.yoelli)、利什曼原虫 (L.major) 和蛔虫幼虫 (T.canis) 过程中的作用。1) 内脏幼虫移行症模型早期阶段犬毛虫感染（第 1 天），观察到独特的肝 T 细胞群，即双阳性 (DP) CD4^+CD8^+ 细胞。此后胸腺外T细胞的比例也升高。2）利什曼病模型感染L.major的小鼠，肝脏中胸腺外T细胞的水平增加。肝脏中这些 T 细胞中 IL-4 的产生能力升高。这些观察结果表明，Th2型免疫应答的诱导在小鼠利什曼病中占主导地位。3)小鼠疟疾模型通过对来自肝脏、脾脏和胸腺的淋巴细胞进行流式细胞术分析，观察到胸腺外T细胞的扩增。它们具有自我反应的禁止克隆和针对寄生红细胞的细胞毒性。TL-2Rbeta^+细胞的缺失导致非致命性疟疾感染的早期恶化。这些数据表明胸腺外T细胞在啮齿动物疟疾感染的红细胞阶段发挥作用。这些结果表明，各器官中扩张的胸腺外T细胞在寄生虫感染期间发挥着重要的保护性免疫作用。